Understanding the pharmacological mechanisms by which cocaine exerts its behavioral effects is essential for medications development for treating cocaine addiction. This proposal will characterize neuropharmacological interactions between dopamine (DA) and glutamate (Glu) in the context of cocaine behavioral pharmacology in nonhuman primates. The role of DA in the behavioral effects of cocaine is widely recognized and associated with its addictive properties. Anatomical substrates and functional interactions between DA and Glu have also been established. Glu has increasingly been implicated in the behavioral effects of cocaine in rodent models. Extrasynaptic Glu, originating from the cystine-glutamate transporter, regulates dopamine function in the mesolimbic pathway. This proposal hypothesizes that glutamatergic regulation of DA occurs via metabotropic glutamate receptors 2/3 (mGluR2/3). The proposed experiments will characterize the consequences of manipulating the transporter and mGluR2/3 on the neuropharmacological and behavioral effects of cocaine. Results from these experiments will evaluate the effectiveness of the transporter and mGluR2/3 as potential targets for cocaine medications development. [unreadable] [unreadable] [unreadable]